Inhibitors of Cyclophilin A: Current and Anticipated Pharmaceutical Agents for Inflammatory Diseases and Cancers
Abstract
:1. Introduction
2. Cyclic Peptides as Cyclophilin A Inhibitors
2.1. Cyclosporin A (CsA)
2.2. Cyclolinopeptides and the Analogues
2.3. Cyclosporin A Derivatives
2.4. Cyclosporin A Analogues
2.4.1. SCY-635
2.4.2. [Me-Ile-4]cyclosporine (NIM811)
2.4.3. Alisporivir (Debio-025)
2.5. Sanglifehrin A (SFA)—A Natural Product
2.6. Cyclosporin O (CsO)—A Natural Macrocycle
3. Small Molecular Inhibitors of Cyclophilin A
3.1. Quinoxaline Derivatives
3.2. Cyclophilin A Inhibitor 239836
3.3. Aryl 1-Indanylketones
3.4. Dimedone Analogues
3.5. Gracilins—Natural Diterpenes Derivative
3.6. Dichloro-Benzophenone Derivative—Natural Compound
3.7. Other Novel Small Molecular Inhibitors of Cyclophilin A
4. Peptide Analogues
4.1. Heptapeptides
4.2. N- or C-Terminal Modification of Gag Peptide
4.3. Trp-Gly-Pro (WGP)
4.4. Pseudopeptides
4.5. “Self-Reproduction of Chirality” Analogues
5. Cyclophilin A Inhibitors in Clinical Trials
6. Conclusions and Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Cyclosporin A (CsA, C1) | |||
R1 | R2 | R3 | |
CsA | |||
C8 (Dihydro-CsA) | |||
C9 ([DehydroAla]8-CsA) | |||
C10 ([MeVal]4-CsA) | |||
C11 ([MeAbu]4-CsA) | |||
C12 ([Me(α-methyl)Thr]4-CsA) |
Inhibitor Number | Inhibitor Name | NCT Number | Alone or in Combination | Sponsors | Diseases | Status |
---|---|---|---|---|---|---|
C1 | Cyclosporin A (CsA) | ~381 cancer-related clinical trials in early phase 1 and phases 1, 2, 3 or 4 b | Alone or in combination | Virginia G. Kaklamani, Novartis, Allergan, NCI, MD Anderson Cancer Center, and others | Breast cancer, colon cancer, melanoma, nonmelanoma skin cancer, hematologic cancer, colorectal cancer, and others | Active, recruiting, completed, or terminated |
NCT00983424 (phase 1) | CsA Nab-paclitaxel | Northwestern University, Avon Foundation | Metastatic breast cancer | Completed | ||
NCT00003950 (phase 2) | CsA CPT-11 | NCI, University of Chicago | Metastatic, advanced, or locally recurrent colorectal cancer | Completed | ||
NCT00389870 (phase 3) | CsA plus Irinotecan | University of Leeds | Colorectal cancer | Completed | ||
NCT04979884 (phase 3) | Alone | Alexandria University | COVID-19 | Completed | ||
NCT04392531 (phase 4) | CsA plus SOC c | Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz | COVID-19 | Completed | ||
NCT00979706 (phase 4) | CsA plus HAART c | Hospital Clinic of Barcelona | HIV | Completed | ||
NCT00866684 (phase 4) | CsA as Comparator | Charite University, Berlin, Germany | Skin cancer | Completed | ||
C13 | SCY-635 | NCT01290965 (phase 1) | Alone | Scynexis | Hepatitis C infection | Completed |
NCT01265511 (phase 2) | Alone | Scynexis | Hepatitis C infection | Completed | ||
C14 | NIM811 | NCT00983060 (phase 2) | Alone | Novartis | Chronic hepatitis C Genotype-1 relapse | Completed |
C15 | Alisporivir (Deb 025) | NCT01975337 (phase 1) | Alone | Debiopharm International SA | Kidney failure | Completed |
NCT02173574 (phase 1) | Deb 025, EDP239 | Enanta Pharmaceuticals | Hepatitis C infection | Completed | ||
NCT01860326 (phase 1) | Alone | Debiopharm International SA | Hepatitis C | Completed | ||
NCT01183169 (phase 2) | Deb 025, Peginterferon alfa-2a, Ribavirin | Debiopharm International SA | Hepatitis C infection | Completed | ||
NCT00537407 (phase 2) | Deb 025, Peginterferon alfa-2a, Ribavirin | Debiopharm International SA | Chronic hepatitis C | Completed | ||
NCT02094443 (phase 2) | Deb 025, Ribavirin | Debiopharm International SA | Hepatitis C infection | Completed | ||
NCT01215643 (phase 2) | Deb 025, Peginterferon alfa-2a, Ribavirin | Debiopharm International SA | Hepatitis C infection | Completed | ||
NCT04608214 (phase 2) | Alone | Assistance Publique—Hôpitaux de Paris | SARS-CoV-2 | Completed | ||
NCT02753699 (phase 3) | Alone | DebiopharmInternational SA | Hepatitis C infection | Completed | ||
NCT01318694 (phase 3) | Deb 025, Peginterferon alfa-2a, Ribavirin | Enanta Pharmaceuticals | Hepatitis C infection | Completed |
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Zhao, X.; Zhao, X.; Di, W.; Wang, C. Inhibitors of Cyclophilin A: Current and Anticipated Pharmaceutical Agents for Inflammatory Diseases and Cancers. Molecules 2024, 29, 1235. https://doi.org/10.3390/molecules29061235
Zhao X, Zhao X, Di W, Wang C. Inhibitors of Cyclophilin A: Current and Anticipated Pharmaceutical Agents for Inflammatory Diseases and Cancers. Molecules. 2024; 29(6):1235. https://doi.org/10.3390/molecules29061235
Chicago/Turabian StyleZhao, Xuemei, Xin Zhao, Weihua Di, and Chang Wang. 2024. "Inhibitors of Cyclophilin A: Current and Anticipated Pharmaceutical Agents for Inflammatory Diseases and Cancers" Molecules 29, no. 6: 1235. https://doi.org/10.3390/molecules29061235
APA StyleZhao, X., Zhao, X., Di, W., & Wang, C. (2024). Inhibitors of Cyclophilin A: Current and Anticipated Pharmaceutical Agents for Inflammatory Diseases and Cancers. Molecules, 29(6), 1235. https://doi.org/10.3390/molecules29061235